Primaxin I.M.

Generic Name: Imipenem and Cilastatin
Class: Carbapenems
Chemical Name: [5R - [5α,6α(R*)]] - 6 - (1 - Hydroxyethyl) - 3 - [[2 - (iminomethyl)amino]ethyl]thio] - 7 - oxo - 1 - azabicyclo[3.2.0]hept - 2 - ene - 2carboxylic acid monohydrate mixt. with [R-[R*,S*-(Z)]]-7-[(2-Amino-2-carboxyethyl)thio]-2-[[(2,2-dimethylcyclopropyl) carbonyl]amino]-2-heptenoic acid monosodium salt
Molecular Formula: C₁₂H₁₇N₃O₄S•H₂
CAS Number: 92309-29-0

Introduction

Antibacterial; fixed combination of imipenem (a carbapenem β-lactam antibiotic)^{2 4 5 6 148 196 197 198} and cilastatin^{1 35} (prevents renal metabolism of imipenem by dehydropeptidase I [DHP I]).^{1 2 101 113 125 137 140 141 145 148 196 198}

Uses for Primaxin I.M.

Bone and Joint Infections

Treament of serious bone and joint infections caused by susceptible Staphylococcus aureus (penicillinase-producing strains), S. epidermidis, Enterobacter, or Pseudomonas aeruginosa.^{1 146 164 167 182 256}

Endocarditis

Treatment of endocarditis caused by susceptible S. aureus (penicillinase-producing strains).^{1 146 186} Not considered a preferred or alternative drug for staphylococcal endocarditis.^{a b}

Should not be used for treatment of enterococcal endocarditis.^{103 198 199 210}

Gynecologic Infections

Treatment of gynecologic infections (including mixed aerobic-anaerobic infections) caused by susceptible Enterococcus faecalis, S. aureus (penicillinase-producing strains), S. epidermidis, S. agalactiae (group B streptococci), Enterobacter, E. coli, Garnerella vaginalis, Klebsiella, Proteus, Bacteroides (including B. fragilis), Bifidobacterium, Peptococcus, Peptostreptococcus, and Propionibacterium.^{1 146 176 178}

Intra-abdominal Infections

Treatment of intra-abdominal infections (including mixed aerobic-anaerobic infections) caused by susceptible E. faecalis, S. aureus (penicillinase-producing strains), S. epidermidis, Citrobacter, Enterobacter, E. coli, Klebsiella, Morganella morganii, Proteus, Ps. aeruginosa, Bacteroides (including B. fragilis), Bifidobacterium, Clostridium, Eubacterium, Fusobacterium, Peptococcus, Peptostreptococcus, or Propionibacterium.^{1 164 172 179 256} .

Respiratory Tract Infections

Treatment of lower respiratory tract infections caused by susceptible S. aureus (penicillinase-producing strains), S. pneumoniae, Haemophilus influenzae, H. parainfluenzae, Acinetobacter, Enterobacter, E. coli, Klebsiella, or Serratia marcescens.^{1 164 167 170 172 183 256}

Treatment of pneumonia and bronchitis (as an exacerbation of COPD) caused by susceptible S. pneumoniae.²⁵⁶ Indicated for polymicrobial infections when S. pneumoniae may be involved, but not usually indicated for monobacterial pneumococcal infections.¹ Not considered a drug of first choice for empiric treatment of community-acquired pneumonia (CAP);^{147 193} usually reserved for use in patients with pneumonia who are at risk for Ps. aeruginosa and when anaerobes may be involved.^{147 193 261}

Has been used for treatment of Legionella pneumophila† respiratory tract infections.^{152 154 171 215} Other anti-infectives (e.g., a macrolide or a fluoroquinolone with or without rifampin) generally preferred.^{76 261 304}

Septicemia

Treatment of septicemia caused by susceptible E. faecalis, S. aureus (penicillinase-producing strains), Enterobacter, E. coli, Klebsiella, Ps. aeruginosa, Serratia, or Bacteroides (including B. fragilis).^{1 146 164 167 170 172 181 261}

Skin and Skin Structure Infections

Treatment of serious skin and skin structure infections caused by susceptible S. aureus (penicillinase-producing strains), S. epidermidis, E. faecalis, Acinetobacter, Citrobacter, Enterobacter, E. coli, Klebsiella, M. morganii, P. vulgaris, P. rettgeri, Ps. aeruginosa, or Serratia.^{1 146 164 167 170 172 179 184}

Treatment of serious skin and skin structure infections caused by susceptible Bacteroides (including B. fragilis), Fusobacterium, Peptococcus, or Peptostreptococcus.^{1 179 184}

Urinary Tract Infections (UTIs)

Treatment of complicated and uncomplicated UTIs caused by susceptible E. faecalis, S. aureus (penicillinase-producing strains) , Enterobacter, E. coli, Klebsiella, M. morganii, P. vulgaris, Providencia rettgeri, or Ps. aeruginosa.^{1 146 158 164 167 168 170 172 173 180 261}

Actinomycosis

Has been used for treatment of thoracic actinomycosis†.²⁹¹ Not considered a drug of choice; penicillin G generally preferred for initial treatment of all forms of actinomycosis, including thoracic, abdominal, CNS, and cervicofacial infections.^{76 261 292}

Bacillus Infections

Treatment of invasive infections caused by Bacillus cereus†.^{76 261} Vancomycin considered drug of choice; carbapenems (imipenem or meropenem) or clindamycin are alternatives.²⁶¹

Burkholderia Infections

Treatment of localized or septicemic melioidosis†,^{261 280 281 282 283 284} a potentially life-threatening disease caused by Burkholderia pseudomallei.^{280 282 283} A drug of choice.^{261 280 281 282 283 284 285} B. pseudomallei is difficult to eradicate (relapse of melioidosis is common).^{280 281 283 285}

Altenative for treatment of glanders† caused by B. mallei.²⁶¹

Altenative for treatment of infections caused by B. cepacia†.²⁶¹

Campylobacter Infections

Treatment of systemic infections caused by Campylobacter fetus†;^{261 286} a drug of choice.^{261 286}

Capnocytophaga Infections

Treatment of infections caused by Capnocytophaga canimorsus†.²⁶¹

Optimum regimens for treatment of infections caused by Capnocytophaga have not been identified; some clinicians recommend use of penicillin G^{261 290} or, alternatively, a third generation cephalosporin (cefotaxime, ceftizoxime, ceftriaxone), a carbapenem (imipenem or meropenem), vancomycin, a fluoroquinolone, or clindamycin.²⁶¹

Nocardia Infections

Treatment of infections caused by Nocardia†, including pulmonary nocardiosis caused by N. asteroides and primary cutaneous nocardiosis.^{261 293 294 295} Co-trimoxazole considered drug of first choice for Nocardia infections;^{76 147 261} alternatives include a sulfonamide (e.g., sulfisoxazole) with or without minocycline or amikacin; a tetracycline (e.g., doxycycline, minocycline); a carbapenem (imipenem or meropenem) with or without amikacin; amoxicillin and clavulanate; cycloserine; or linezolid.^{76 147 261}

Rhodococcus Infections

Treatment of infections caused by Rhodococcus equi†; used in conjunction with vancomycin.²⁶¹ Optimum regimens have not been identified;²⁹⁸ combination regimens usually are recommended, including vancomycin given with a fluoroquinolone, rifampin, a carbapenem (imipenem or meropenem), or amikacin.^{261 297 298 299}

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients†.^{265 266 267 268 269 270 271} Used alone or in conjunction with other anti-infectives.^{268 269 271}

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.¹⁴ Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.¹⁴

Primaxin I.M. Dosage and Administration

Administration

Administer by intermittent IV infusion¹ and by deep IM injection.²⁵⁶

IM route should only be used for mild to moderately severe infections;^{256 257 258 259} it is not intended for use in severe and/or life-threatening infections (e.g., sepsis, endocarditis) or in patients with major physiologic impairment (e.g., shock).²⁵⁶ Patients for whom IM therapy is being considered should be selected carefully^{256 257 258 259} since some reported treatment failures and/or recurrences may have been related to the route of administration.^{257 258 259}

The IM suspension should not be given IV.²⁵⁶

ADD-Vantage vials should be used only for IV infusion.¹

For solution and drug compatibility information, see Compatibility under Stability.

IV Infusion

Imipenem solutions for IV infusion should have concentrations ≤5 mg/mL since physical and chemical stability of the drug may be adversely affected at higher concentrations.²¹⁹

If an aminoglycoside is administered concomitantly, the drugs should not be admixed but may be administered from separate containers through the same IV tubing.²¹⁹

Reconstitution and Dilution

Reconstitute infusion bottles containing 250 mg of imipenem and 250 mg of cilastatin or 500 mg of imipenem and 500 mg of cilastatin with 100 mL of a compatible IV solution¹ to provide solutions containing 2.5 or 5 mg/mL of each drug, respectively.²¹⁹ Shake until a clear solution is obtained.¹

Alternatively, vials containing 250 mg of imipenem and 250 mg of cilastatin or 500 mg of imipenem and 500 mg of cilastatin may be initially suspended with a portion of a compatible IV solution and then the resulting suspension of drug added to the remaining IV solution to a volume of 100 mL.¹ A suggested procedure for preparing an initial suspension is to add approximately 10 mL from a 100-mL container of the IV solution to the vial of drug.¹ The resulting initial suspension should be shaken well and then transferred to the IV solution container.¹ To ensure complete transfer of the vial contents, an additional 10 mL from the IV solution container should be added to the vial and transferred back to the IV solution container.¹

ADD-Vantage vials should be reconstituted according to the manufacturer’s directions with the diluent provided.¹

Rate of Administration

The rate of IV infusion depends on the dose.^{1 164} If nausea and/or vomiting occur during administration, the rate of IV infusion may be decreased.^{1 164}

In adults, each 125-, 250- or 500-mg dose of imipenem should be infused over 20–30 minutes and each 1-g dose should be infused over 40–60 minutes.^{1 164}

In pediatric patients, doses of ≤500 mg should be given by IV infusion over 15–30 minutes and doses >500 mg should be given by IV infusion over 40–60 minutes.¹

IM Administration

IM suspensions are administered by deep IM injection into a large muscle mass (such as the gluteal muscle or lateral aspect of the thigh) with a 21-gauge, 2-inch needle.²⁵⁶ Use aspiration to avoid inadvertent injection into a blood vessel.²⁵⁶

Reconstitution and Dilution

IM injections are reconstituted with lidocaine hydrochloride 1% injection (without epinephrine).²⁵⁶ Add 2 or 3 mL of the diluent to a vial containing 500 or 750 mg of imipenem, respectively.²⁵⁶ The vial should be agitated well to form a suspension and the entire contents of the vial withdrawn for IM injection.²⁵⁶

Dosage

Available as fixed-combination containing imipenem monohydrate and cilastatin sodium; dosage generally expressed in terms of the imipenem content (as anhydrous imipenem).^{1 35 256}

To minimize risk of seizures, closely adhere to dosage recommendations, especially in patients with factors known to predispose to seizure activity; dosage adjustment recommended for patients with advanced age and/or renal impairment.¹ Anticonvulsant therapy should be continued in patients with existing seizure disorders.¹ (See CNS Effects under Cautions.)

Duration of therapy depends on type and severity of infection.²⁵⁶ Safety and efficacy of the IM route for >14 days have not been established.²⁵⁶

Pediatric Patients

General Dosage for Neonates

IV

Neonates <1 week of age weighing ≥1.5 kg: 25 mg/kg every 12 hours.¹

Neontes 1–4 weeks of age weighing ≥1.5 kg: 25 mg/kg every 8 hours.¹

General Dosage for Infants and Children

IV

Children 1–3 months of age weighing ≥1.5 kg: 25 mg every 6 hours.¹

Children ≥3 months of age: 15–25 mg/kg every 6 hours.¹

Mild to Moderately Severe Infections

Gynecologic, Lower Respiratory Tract, or Skin and Skin Structure Infections

IM

Children ≥12 years of age: 500 or 750 mg every 12 hours.²⁵⁶

Intra-abdominal Infections

IM

Children ≥12 years of age: 750 mg every 12 hours.²⁵⁶

Adults

Recommended IV adult dosages are for adults weighing ≥70 kg.¹ Modification of dosage is recommended for patients weighing <70 kg.¹ (See Adults with Low Body Weight under Dosage and Administration.)

Mild Infections

Fully Susceptible Aerobic or Anaerobic Bacteria

IV

Adults weighing ≥70 kg: 250 mg every 6 hours (1 g daily).¹

Moderately Susceptible Aerobic or Anaerobic Bacteria

IV

Adults weighing ≥70 kg: 500 mg every 6 hours (2 g daily).¹

Moderately Severe Infections

Fully Susceptible Aerobic or Anaerobic Bacteria

IV

Adults weighing ≥70 kg: 500 mg every 8 hours (1.5 g daily) or 500 mg every 6 hours (2 g daily).¹

Moderately Susceptible Aerobic or Anaerobic Bacteria

IV

Adults weighing ≥70 kg: 500 mg every 6 hours (2 g daily) or 1 g every 8 hours (3 g daily).¹

Severe, Life-threatening Infections

Fully Susceptible Aerobic or Anaerobic Bacteria

IV

Adults weighing ≥70 kg: 500 mg every 6 hours (2 g daily).¹

Moderately Susceptible Aerobic or Anaerobic Bacteria

IV

Adults weighing ≥70 kg: 1 g every 6 hours (4 g daily) or 1 g every 8 hours (3 g daily).¹

Urinary Tract Infections (UTIs)

Uncomplicate UTIs

IV

Adults weighing ≥70 kg: 250 mg every 6 hours (1 g daily)¹ .

Complicated UTIs

IV

Adults weighing ≥70 kg: 500 mg every 6 hours (2 g daily).¹

Mild to Moderately Severe Infections

Gynecologic, Lower Respiratory Tract, or Skin and Skin Structure Infections

IM

500 or 750 mg every 12 hours.²⁵⁶

Intra-abdominal Infections

IM

750 mg every 12 hours.²⁵⁶

Empiric Therapy in Febrile Neutropenic Patients†

IV

500 mg every 6 hours (1 g daily).^{265 266 268}

Prescribing Limits

Pediatric Patients

IV

2 g daily in those with infections caused by fully susceptible bacteria or 4 g daily in those with infections caused by moderately susceptible bacteria (e.g., some strains of Ps. aeruginosa).¹ Higher dosage (up to 90 mg/kg daily in older children) has been used in some cystic fibrosis patients.¹

Adults

IV

50 mg/kg daily or 4 g daily, whichever is lower.¹

IM

1.5 g daily.²⁵⁶

Special Populations

Renal Impairment

Infections in Adults

IV

Dosage adjustments recommended in adults with Cl_cr <70 mL/minute per 1.73 m².¹ Serum creatinine concentrations alone may not be sufficiently accurate to assess the degree of renal impairment; dosage preferably should be based on the patient’s measured or estimated Cl_cr.^{1 256}

Manufacturer makes the following recommendations for dosage in adults with Cl_cr <70 mL/minute per 1.73 m² and/or body weight <70 kg.¹ (See Table 1.)

Table 1. Reduced Intravenous Dosage of Imipenem and Cilastatin Sodium IV in Adult Patients with Impaired Renal Function and/or Body Weight < 70 kg

	If Total Recommended Daily Dose is:
	1 g/day	1.5 g/day	2 g/day
	and creatinine clearance (mL/min/1.73 m2) is:
	≥71	41–70	21–40	6–20	≥71	41–70	21–40	6–20	≥71	41–70	21–40	6–20
and Body Weight (kg) is:	then the reduced dosage regiment (mg) is:
≥70	250 q6h	250 q8h	250 q12h	250 q12h	500 q8h	250 q6h	250 q8h	250 q12h	500 q6h	500 q8h	250 q6h	250 q12h
60	250 q8h	125 q6h	250 q12h	125 q12h	250 q6h	250 q8h	250 q8h	250 q12h	500 q8h	250 q6h	250 q8h	250 q12h
50	125 q6h	125 q6h	125 q8h	125 q12h	250 q6h	250 q8h	250 q12h	250 q12h	250 q6h	250 q6h	250 q8h	250 q12h
40	125 q6h	125 q8h	125 q12h	125 q12h	250 q8h	125 q6h	125 q8h	125 q12h	250 q6h	250 q8h	250 q12h	250 q12h
30	125 q8h	125 q8h	125 q12h	125 q12h	125 q6h	125 q8h	125 q8h	125 q12h	250 q8h	125 q6h	125 q8h	125 q12h

Table 1. Renal Impairment Dosage (cont'd)

	If Total Recommended Daily Dose is:
	3 g/day	4 g/day
	and creatinine clearance (mL/min/1.73 m2) is:
	≥71	41–70	21–40	6–20	≥71	41–70	21–40	6–20
and Body Weight (kg) is:	then the reduced dosage regiment (mg) is:
≥70	1000 q8h	500 q6h	500 q8h	500 q12h	1000 q6h	750 q8h	500 q6h	500 q12h
60	750 q8h	500 q8h	500 q8h	500 q12h	1000 q8h	750 q8h	500 q8h	500 q12h
50	500 q6h	500 q8h	250 q6h	250 q12h	750 q8h	500 q6h	500 q8h	500 q12h
40	500 q8h	250 q6h	250 q8h	250 q12h	500 q6h	500 q8h	250 q6h	250 q12h
30	250 q6h	250 q8h	250 q8h	250 q12h	500 q8h	250 q6h	250 q8h	250 q12h

Impenem should be used in patients undergoing hemodialysis only when potential benefits outweigh the potential risk of drug-induced seizures.^{1 219} If used IV in hemodialysis patients, a supplemental dose of the drug should be given after each dialysis period^{1 120 126 140} and at 12-hour intervals thereafter.¹ In addition, patients should be monitored closely for adverse CNS effects (e.g., confusion, myoclonic activity, seizures), especially those with CNS disease.¹

Patients with Cl_cr ≤5 mL/minute per 1.73² should not receive imipenem and cilastatin sodium IV unless hemodialysis is instituted within 48 hours.¹

IM

IM route should not be used in patients with Cl_cr <20 mL/minute per 1.73 m².²⁵⁶

Infections in Pediatric Patients

IV

Not recommended in pediatric patients weighing <30 kg with impaired renal function.¹

Adults with Low Body Weight

Dosage adjustment recommended when IV imipenem used in adults with body weight <70 kg.¹ IV dosage recommended for these adults is the same as that recommended for adults with renal impairment.¹ (See Tables.)

Geriatric Patients

No dosage adjustments except those related to renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Primaxin I.M.

Contraindications

• 
  

  Hypersensitivity to any ingredient in the formulation.^{1 256}

  
  


• 
  

  IM injections are prepared using lidocaine hydrochloride and are contraindicated in patients with known hypersensitivity to local anesthetics of the amide type and in patients with severe shock or heart block.²⁵⁶

  
  

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organism.^{1 256} Careful observation of the patient is essential.^{1 256} Institute appropriate therapy if superinfection occurs.^{1 256}

Treatment with anti-infectives may permit overgrowth of clostridia.^{1 256 305 306 307 308 309} Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.^{1 256}

Some mild cases of C. difficile-asssociated diarrhea and colitis may respond to discontinuance alone.^{1 256 305 306 307 308 309} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.^{1 256 305 306 307 308 309}

CNS Effects

Seizures and other CNS effects (e.g., confusional states, myoclonic activity) have occurred.^{1 256} Reported most frequently in those with CNS disorders (e.g., brain lesions, history of seizures) and/or renal impairment, but also reported in patients with no recognized or documented underlying CNS disorder or renal impairment.^{1 256}

Do not exceed recommended dosage, especially in those with known factors that predispose to seizures.^{1 256} Anticonvulsant therapy should be continued in those with known seizure disorders.^{1 256}

Patients with Cl_cr ≤20 mL/minute per 1.73 m₂ (even if undergoing hemodialysis) are at increased risk of seizures if recommended doses are exceeded.¹ For patients undergoing hemodialysis, IV imipenem should be used only if benefits outweigh the potential risk of seizures.¹

If focal tremors, myoclonus, or seizures occur, evaluate the patient neurologically, initiate anticonvulsant therapy if necessary, and determine whether imipenem dosage should be decreased or the drug discontinued.^{1 256}

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis) reported with β-lactams.^{1 256}

If hypersensitivity occurs, discontinue imipenem and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).^{1 256}

Cross-Hypersensitivity

Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and other β-lactams.^{1 256}

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to imipenem, cephalosporins, penicillins, or other drugs.^{1 256}

General Precautions

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.^{1 256}

Sodium Content

IV preparations contain approximately 1.6 mEq (37.5 mg) of sodium per 500 mg of imipenem;¹ IM preparations contain approximately 1.4 mEq (32 mg) of sodium per 500 mg of imipenem.¹

Ps. aeruginosa Infections

Because resistant strains of Ps. aeruginosa have emerged during imipenem and cilastatin therapy,^{137 153 157 162 163 164 171 173 183 191 198 222 240} most clinicians recommend that an aminoglycoside be used concomitantly whenever the drug is used in the treatment of serious infections known or suspected to be caused by Ps. aeruginosa.^{137 146 153 157 162 163 164 173 174 183 191 196 198 210 240}

Meningitis and Other CNS Infections

Safety and efficacy for treatment of meningitis has not been established.¹ High incidence of seizures reported in children 3 months to 12 years of age who received the drug for empiric treatment of bacterial meningitis.²⁴²

Specific Populations

Pregnancy

Category C.^{1 256}

Lactation

Imipenem distributed into milk.²¹⁹ Use with caution.^{1 256}

Pediatric Use

Safety and efficacy of IM imipenem and cilastatin have not been established in children <12 years of age.²⁵⁶

Adverse effects reported with IV imipenem in neonates and children are similar to those reported in adults.¹ Seizures have been reported in neonates and children ≤3 months of age; a high incidence of seizures reported in children 3 months to 12 years of age who received the drug for empiric treatment of bacterial meningitis.^{1 242} Because of the risk of seizures, imipenem should not be used in pediatric patients with CNS infections.¹

Data are insufficient to date regarding use of imipenem in pediatric patients with impaired renal function who weigh <30 kg; the drug should not be used in these children.¹

Imipenem solutions that have been reconstituted with bacteriostatic water for injection containing benzyl alcohol should not be used in neonates or children ≤3 months of age.^{1 272 273} Although a causal relationship not established, injections preserved with benzyl alcohol have been associated with toxicity in neonates.^{272 273}

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.^{1 256}

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.^{1 256} Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.^{1 256}

No dosage adjustments except those related to renal function.^{1 256} (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Half-lives of both imipenem and cilastatin prolonged in patients with impaired renal function.^{120 126 185}

Patients with renal impairment are at increased risk for adverse CNS effects (e.g., seizures), especially if usual dosage is exceeded.¹ Do not use in patients undergoing hemodialysis unless benefits outweigh the possible risk of drug-induced seizures.^{1 219} Patients with Cl_cr ≤5 mL/minute per 1.73 m² should not receive IV imipenem and cilastatin IV unless hemodialysis is instituted within 48 hours.¹ If used IV in hemodialysis patients, a supplemental dose of the drug should be given after each dialysis period^{1 120 126 140} and at 12-hour intervals thereafter.¹ In addition, patients should be monitored closely for adverse CNS effects (e.g., confusion, myoclonic activity, seizures), especially those with CNS disease.¹

Dosage adjustment recommended in adults with Cl_cr ≤70 mL/minute.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (nausea, diarrhea, vomiting); CNS effects; eosinophilia; local reactions (phlebitis/thrombophlebitis).^{1 256}

Interactions for Primaxin I.M.

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Aminoglycosides	In vitro evidence of additive or synergistic antibacterial effects against E. faecalis, S. aureus, and Listeria monocytogenes13 19 103 106 109 139
β-Lactam anti-infectives	In vitro evidence of antagonism with other β-lactam anti-infectives against Enterobacteriaceae and Ps. aeruginosa3 13 54 102 107 111 137 198 240 244 247	Clinical importance unclear; probably should not be used in conjunction with other β-lactam anti-infectives54 102 210 240
Chloramphenicol	In vitro evidence of antagonism with chloramphenicol against K. pneumoniae104 111	If used concomitantly, consider administering chloramphenicol a few hours after imipenem104
Co-trimoxazole	In vitro evidence of synergistic antibacterial effect against Nocardia asteroides108	Clinical importance unclear108
Ganciclovir	Seizures reported with concomitant use1 253 254	Use concomitantly only when potential benefits outweigh the possible risks1 253 254
Probenecid	Increased cilastatin concentrations and prolonged half-life125 140	Concomitant use not recommended1 256
Tests for glucose	Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution132	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)132

Primaxin I.M. Pharmacokinetics

Absorption

Bioavailability

Neither imipenem nor cilastatin appreciably absorbed from GI tract; must be given parenterally.^{125 143}

Imipenem incompletely absorbed following IM administration;^{217 256} peak plasma concentrations of imipenem attained within 2 hours and peak plasma concentrations of cilastatin attained within 1 hour.²⁵⁶ Bioavailabilities of imipenem and cilastatin following IM administration range from 60–75 and 95–100%, respectively.^{217 256}

Following IV administration, plasma imipenem concentrations during the first 2 hours exceed those attained following IM administration of the same doses; however, plasma imipenem concentrations achieved 4–6 hours after an IM dose exceed those after an IV dose and persist longer.²⁵⁶

Distribution

Extent

Following IV administration, imipenem distributed into saliva, ²⁰⁸ sputum, ^{1 208 215} aqueous humor, ^{1 215} bone, ^{1 182 208 215} bile, ^{1 215} reproductive organs, ¹ myometrium, ²¹⁵ endometrium, ²¹⁵ heart valve, ²¹⁵ intestine, ²¹⁵ and pleural, ¹ interstitial, ¹ blister, ¹⁴² and wound^{208 215} fluids.

Only low imipenem concentrations distribute into CSF following IV administration.^{1 117 188 205}

Both imipenem and cilastatin cross the placenta and are distributed into cord blood and amniotic fluid.^{209 251} Imipenem is distributed into milk.²¹⁹

Plasma Protein Binding

Imipenem is 13–21%^{1 125 256} and cilastatin is approximately 40%^{1 256} bound to serum proteins.

Elimination

Metabolism

If imipenem is administered alone, the drug is partially hydrolyzed in kidneys by dehydropeptidase I (DHP I) to a microbiologically inactive metabolite.^{1 113 125 140 143 148}